Application of failure mode and effects analysis in quality by design approach for formulation of carvedilol compression coated tablets

Compression coating technique has been used in formulation of chronotherapeutic drug delivery systems with pulsatile carvedilol release with polyethylene oxide as controlling release agent. FMEA, risk analysis tool, was applied within Quality by Design approach with aim to detect process and formulation parameters affecting the carvedilol release profile from compression coated tablets. It gives Risk Priority Numbers (RPNs) for each failure mode. Also, using experimental designs, statistical significance of the formulation parameters influence was estimated. High RPNs in case of the lag time as critical quality attribute (CQA) was obtained for polymer molecular weight, compression of coat and low concentration of sodium chloride. For percent of released carvedilol from coated tablets (Q), second CQA, RPNs were high for low concentration of sodium chloride, sodium starch glycolate and crospovidone, polymer molecular weight and also for compression of the tablet coat. Experiments performed according to experimental plans, showed statistically significant influence of Polyox® WSR N60K and sodium chloride concentration on lag time, and concentration of polymer, sodium chloride, mannitol and type of superdisintegrant on Q. These studies demonstrate that FMEA may be a useful tool for Formulation by Design of compression coated tablets.

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